Throughout the academic year, the Center for the Study of Human Health (CSHH) brings Emory and the Atlanta community a host of health-related events. From the film series, Health Screenings, to the Speaker's Series, CSHH invites those interested in learn about emerging health researcher or take a deeper inspection into the ways health is represented to our communities. Last Spring, Dr. Tessa Roseboom, professor of Early Development and Health at the Academic Medical Center at the University of Amsterdam, delivered a lecture at Emory on her research into the effect of prenatal exposure to famine on future health. To investigate this relationship, Roseboom looked back at the extensive birth records kept during the Dutch Hunger Winter.

The Dutch famine took place in 1944-1945, at the end of World War II, in the German-occupied part of the Netherlands. During that winter, a German blockade cut off food and fuel shipments to many parts of the country, and the 4.5 million people in the affected areas suffered from severe malnutrition and starvation.

Roseboom and her research team were interested in the present-day health of people conceived during the hunger winter, so they traced all the babies born around the same time in one hospital in Amsterdam, and at the age of 50 started investigating those men and women.

“What we found was really quite striking,” Roseboom said. “People conceived during the famine who were exposed to a very poor maternal diet when they had just been conceived, had double the rates of cardiovascular disease, already at the age of 50. They were more obese, they had higher cholesterol levels, higher blood pressure levels, they felt less healthy, and more of them died of cardiovascular disease.”

According to Roseboom, these findings revealed several lessons.

“Prenatal malnutrition does have long-term consequences,” Roseboom said, “Even though the absolute amount of nutrients an embryo needs is tiny. Lots of people initially told me ‘but the fetus is the perfect parasite, is just takes whatever it needs,’ but that’s not true. The fetus is responsive to the environment and the environment does have lasting consequences.”

For Roseboom, one symbol of the importance of prenatal and postnatal health is the bonsai tree. Bonsai trees, she pointed out, have the same genetic makeup as their larger tree counterparts, but because they are grown in a very small pot, their resources are restricted and they are not able to grow to their full potential. Roseboom points out that the same concept applies to humans—fetuses who are exposed to famine during gestation suffer restrictions on organ growth and development, causing very real health consequences for those people later in life.

In particular, Roseboom noticed that the effects of famine are most significant when the fetus is exposed early in gestation. “We know that in the first trimester all of the organs are laid down,” Roseboom said, “So it’s not surprising that especially exposure in early gestation had so many effects on brain, on heart, on liver, on lungs, and different organs.”

Roseboom addresses several possible mechanisms through which these health outcomes develop, such as a greater change in blood pressure in response to stress, impaired insulin sensitivity, structural differences in the brain, and preference for fatty foods.

Bonsai tree in a small pot. Photo by: Jenn via Flickr

​Contrary to what they might have expected, Roseboom’s team found that the effects of famine are independent of babies’ size at birth. Many mothers carrying babies during the famine had proper nutrition during the second and third trimesters, so they gave birth to normal-weight babies.

“Based on their size at birth you wouldn’t have thought that they had actually been affected, but actually, at the age of 50, they were the ones who were more obese, had more atherogenic lipid profiles, and died more from heart disease.”

This finding revealed that in future studies of pregnant women, interventions should not be abandoned just because they do not have an effect on birth weight.

“Even if interventions don’t have any short-term effects, they might have long-term effects,” Roseboom said.

Another lesson Roseboom took from the Hunger Winter study was that in order to prevent chronic degenerative diseases such as heart disease and diabetes, interventions need to start before conception.

“I think that will have a huge impact not only on preventing cardiovascular disease,” Roseboom said. “But also in improving the chances of people reaching their full potential in terms of health, development, and academic achievements. It’s really very important to invest in a good start in life.”

The importance of early interventions hinges on Roseboom’s finding that prenatal exposure to famine affects not only that first generation of babies, but the babies’ future children as well. She reminds us that every one of us has been not only in our mother’s womb, but also in our grandmother’s womb.

“It’s something you learn in secondary school, that every girl is born with all the oocytes she’ll ever have,” Roseboom said. “The oocytes in my mother’s ovaries were there at the time [of the Dutch famine]. So the egg that made me has actually been directly exposed to the famine.”

A group of children during the Dutch Hunger Winter.​Photo by: Kelly Short, via Flickr

While the Hunger Winter directly affected Roseboom’s own parents and grandparents, she reminds us that this is not the reason she became interested in the study.

“That would seem sort of logical, but I don’t think that was [the reason], because everyone in my generation had parents who were born around the time of the Dutch famine and not everyone is doing this research,” she said.

Rather, Roseboom’s interest in prenatal development stemmed from her interest in biology.

“I studied biology and was really interested in reproduction,” Roseboom said. “I started working at an IVF clinic to gain some research experience, and I just looked through the microscope at eggs being fertilized and wondered: these embryos are actually created in a petri dish rather than somewhere in the ovary. Couldn’t that have potential consequences for development and growth of these children?”

While writing a plan to investigate the long-tem consequences of IVF, Roseboom realized that as a biologist, she did not have the biostatistics and epidemiology skills she needed.

“So I went on to take courses in that area," Roseboom said. "I was later asked to apply for a PhD studentship on the Dutch Famine, which was slightly different but still had, of course, a lot to do with prenatal exposures and long-term consequences.”

Photo by: Anne Geddes via Flickr

​Despite her success, Roseboom has encountered a variety of challenges in researching and developing interventions, including getting funding for studies with such a long-term vision as preventing myocardial infarctions in the next two generations.

“Trying to prevent something is a very promising strategy,” Roseboom said, “but it’s not as exciting. The difficult thing is that success is when nothing happens, and that’s a challenging message to get across.”

Another challenge has been getting women to participate. According to Roseboom, many women may not see the value in participating in these studies because they do not realize how important their health and well-being is not only for themselves, but also for future generations.

“Being a mother of children myself, I know it’s a busy life having a job and a family and also participating in this study is a bit too much,” Roseboom said. “So what we try to do is make it as easy as possible for women to participate in studies.”

Roseboom still works on the Dutch Hunger Winter study, but much more of her time is devoted to a variety of clinical studies, and projects focusing on translating her findings to the current situation in the West. Some of her current projects include researching the long-term effects of different environmental conditions during IVF treatment, designing interventions to help pregnant women suffering from nausea and vomiting, investigating the potential effects of Ramadan fasting during pregnancy, developing a pre-conception lifestyle intervention aiming to prevent heart disease in women and their children, and talking to aid organizations about hopes to prioritize feeding women and children in poorer countries, in order to influence the health of future generations.

Roseboom advises students interested in public health and health research to dare to be different.

“When I was working on the Dutch Famine,” Roseboom said, “People came to me and said ‘Really? Do you think something that happened 50 years ago is going to have any relevant effect today?’ I’m so happy that there were people supporting me to go ahead and to it, because otherwise I wouldn’t be here talking to you today. I think daring to be different is really what will help public health move forward, and I think if we could inspire young public health researchers to really think out of the box, that could make a big change.”

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